Structural highlights
Function
[ACTPC_ACTFR] Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers.[1]
Publication Abstract from PubMed
The recent high-resolution structure of the toxin FraC derived from the sea anemone Actinia fragacea has provided new insight into the mechanism of pore formation by actinoporins. In this work, we report two new crystal forms of FraC in its oligomeric prepore conformation. Together with the previously reported structure, these two new structures reveal that ring-like nonamers of the toxin assemble into compact two-dimensional hexagonal arrays. This supramolecular organization is maintained in different relative orientations adopted by the oligomers within the crystal layers. Analyses of the aggregation of FraC pores in both planar and curved (vesicles) model membranes show similar 2D hexagonal arrangements. Our observations support a model in which hexagonal pore-packing is a clustering mechanism that maximizes toxin-driven membrane damage in the target cell.
Pores of the toxin FraC assemble into 2D hexagonal clusters in both crystal structures and model membranes.,Mechaly AE, Bellomio A, Morante K, Agirre J, Gil-Carton D, Valle M, Gonzalez-Manas JM, Guerin DM J Struct Biol. 2012 Jun 21. PMID:22728830[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bellomio A, Morante K, Barlic A, Gutierrez-Aguirre I, Viguera AR, Gonzalez-Manas JM. Purification, cloning and characterization of fragaceatoxin C, a novel actinoporin from the sea anemone Actinia fragacea. Toxicon. 2009 Nov;54(6):869-80. doi: 10.1016/j.toxicon.2009.06.022. Epub 2009 Jun, 27. PMID:19563820 doi:10.1016/j.toxicon.2009.06.022
- ↑ Mechaly AE, Bellomio A, Morante K, Agirre J, Gil-Carton D, Valle M, Gonzalez-Manas JM, Guerin DM. Pores of the toxin FraC assemble into 2D hexagonal clusters in both crystal structures and model membranes. J Struct Biol. 2012 Jun 21. PMID:22728830 doi:10.1016/j.jsb.2012.06.003
